FDA Accepts Supplemental Biologics License Application (sBLA), Assigns Priority Review to Merck’s KEYTRUDA® (pembrolizumab) for Treatment of Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma (PMBCL)

Data for KEYTRUDA in Patients with Relapsed or Refractory PMBCL Show Overall Response Rate of 41 Percent in Difficult-to-Treat Patient Population

Findings from KEYNOTE-170 Presented at 59th American Society of Hematology (ASH) Annual Meeting

KENILWORTH, NJ, USA I December 11, 2017 I Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced findings from the phase 2 KEYNOTE-170 trial investigating the use of KEYTRUDA® (pembrolizumab), the company’s anti-PD-1 therapy, in the cohort of patients with relapsed or refractory primary mediastinal large B-cell lymphoma (PMBCL), a type of non-Hodgkin lymphoma. In the PMBCL cohort of KEYNOTE-170, KEYTRUDA demonstrated an overall response rate (ORR) of 41 percent (n=12/29), including a 24 percent (n=7/29) complete response rate and a 17 percent (n=5/29) partial response rate, in patients who relapsed after or were refractory to autologous stem cell transplant (ASCT), or were ineligible for ASCT and failed two or more prior lines of therapy. These data were presented at the 59th American Society of Hematology (ASH) Annual Meeting in Atlanta on Sunday, Dec. 10 (Abstract #2833).

“There is a significant unmet need for patients with relapsed or refractory primary mediastinal large B-cell lymphoma,” said Pier Luigi Zinzani, M.D., Ph.D., associate professor of hematology, Institute of Hematology “L. e A. Seràgnoli,” University of Bologna. “These encouraging results represent another step in understanding the potential of KEYTRUDA to help these patients who have already tried and progressed on prior therapies.”

Based on data from KEYNOTE-170 and the phase 1b KEYNOTE-013 trial, which is evaluating the safety, tolerability and efficacy of KEYTRUDA monotherapy in patients with various blood cancers, the U.S. Food and Drug Administration (FDA) has accepted for review a supplemental Biologics License Application (sBLA) for KEYTRUDA (pembrolizumab) for the treatment of adult and pediatric patients with refractory primary mediastinal B-cell lymphoma, or who have relapsed after two or more prior lines of therapy. The FDA granted Priority Review status with a PDUFA, or target action, date of April 3, 2018. In January 2017, KEYTRUDA was granted Breakthrough Therapy Designation by the FDA for this indication.

“These findings in patients with PMBCL are promising for a rare lymphoma that affects mainly young adults and has few effective treatment options in the relapsed or refractory treatment setting,” said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “If approved by the FDA, this would be our second blood cancer indication for KEYTRUDA, following FDA approval for certain patients with classical Hodgkin Lymphoma earlier this year. The acceptance of our sBLA reinforces our ongoing commitment to finding new treatment advances in hematology.”

The KEYTRUDA hematology program includes more than 50 ongoing studies – including company sponsored, investigator sponsored and collaborative studies; several of these are registration-enabling trials.

Data from KEYNOTE-170 at ASH (Abstract #2833)

KEYNOTE-170 is an ongoing, non-randomized, two-cohort, multicenter, phase 2 study evaluating the efficacy and safety of KEYTRUDA (200 mg fixed dose every three weeks) in patients with relapsed or refractory PMBCL and in patients with relapsed or refractory Richter syndrome. The PMBCL cohort enrolled patients who relapsed after or were refractory to ASCT, or were ineligible for ASCT; patients ineligible for ASCT had to have relapsed or refractory disease after two or more lines of prior therapy. The primary endpoint was ORR by blinded independent central review; key secondary endpoints included duration of response and safety and tolerability.

In the efficacy population (n=29), ORR was 41 percent (n=12) (95% CI, 24-61), with a complete response rate of 24 percent (n=7) (95% CI,10-44) and a partial response rate of 17 percent (n=5) (95% CI, 6-36). Median duration of follow-up was 10.5 months (range: 0.1-17.7). Median time to response was 2.8 months (range: 2.4-5.5). Median duration of response was not reached (range: 1.1+ to 13.6+ months).

Treatment-related adverse events (TRAEs) were consistent with previously reported safety data for KEYTRUDA. Of the 53 patients evaluated for safety, 57 percent (n=30) experienced TRAEs, including 21 percent (n=11) who experienced Grade 3-4 TRAEs. The most common TRAEs (greater than or equal to 5%) were neutropenia (n=11), hypothyroidism (n=4), asthenia (n=3) and pyrexia (n=3). Immune-mediated adverse events of all grades occurred in 11 percent (n=6) of patients; these include hypothyroidism (n=4), hyperthyroidism (n=2), pneumonitis (n=1) and thyroiditis (n=1). There were no treatment-related deaths.

About Primary Mediastinal Large B-Cell Lymphoma

PMBCL is a sub-type of diffuse large B-cell lymphoma (a type of non-Hodgkin lymphoma) that starts in the space between the lungs, called the mediastinum. PMBCL mainly affects young adults (with a median age of 35), and occurs slightly more often in women. PMBCL accounts for two to four percent of all non-Hodgkin lymphomas in the U.S.

About KEYTRUDA® (pembrolizumab) Injection 100mg

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program, which currently involves more than 650 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

KEYTRUDA (pembrolizumab) Indications and Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA, as a single agent, is indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.

KEYTRUDA, as a single agent, is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving KEYTRUDA (pembrolizumab).

KEYTRUDA, in combination with pemetrexed and carboplatin, is indicated for the first-line treatment of patients with metastatic nonsquamous NSCLC. This indication is approved under accelerated approval based on tumor response rate and progression-free survival. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

When administering KEYTRUDA in combination with chemotherapy, KEYTRUDA should be administered prior to chemotherapy when given on the same day. See also the Prescribing Information for pemetrexed and carboplatin.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after three or more prior lines of therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In adults with cHL, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. In pediatric patients with cHL, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Urothelial Carcinoma

KEYTRUDA (pembrolizumab) is indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

KEYTRUDA is also indicated for the treatment of patients with locally advanced or metastatic urothelial carcinoma who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

In locally advanced or metastatic urothelial carcinoma, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

  • solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, or
  • colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The safety and effectiveness of KEYTRUDA in pediatric patients with MSI-H central nervous system cancers have not been established.

In adult patients with MSI-H cancer, KEYTRUDA is administered at a fixed dose of 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. In children with MSI-H cancer, KEYTRUDA is administered at a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. The recommended dose of KEYTRUDA (pembrolizumab) is 200 mg every three weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Our Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology medicines to help people with cancer worldwide. At Merck, helping people fight cancer is our passion and supporting accessibility to our cancer medicines is our commitment. Our focus is on pursuing research in immuno-oncology and we are accelerating every step in the journey – from lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the potential of immuno-oncology with one of the fastest-growing development programs in the industry. We are currently executing an expansive research program evaluating our anti-PD-1 therapy across more than 30 tumor types. We also continue to strengthen our immuno-oncology portfolio through strategic acquisitions and are prioritizing the development of several promising immunotherapeutic candidates with the potential to improve the treatment of advanced cancers.

For more information about our oncology clinical trials, visit www.merck.com/clinicaltrials.

About Merck

For more than a century, Merck, a leading global biopharmaceutical company known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world’s most challenging diseases. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to advance the prevention and treatment of diseases that threaten people and communities around the world - including cancer, cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease and infectious diseases including HIV and Ebola. For more information, visit www.merck.com and connect with us on TwitterFacebookInstagram, YouTube and LinkedIn.

SOURCE: Merck

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